tbuckley/cabot-search huggingface dataset:
Clinical utility of comprehensive genomic profiling in patients with unresectable primary liver cancer.
Authors: Shun Ishido, Kaoru Tsuchiya, Keito Suzuki, Naoki Uchihara, Yuki Tanaka, Haruka Miyamoto, Michiko Yamada, Taisei Keitoku, Hiroaki Matsumoto, Tsubasa Nobusawa, Mayu Higuchi, Kenta Takaura, Shohei Tanaka, Chiaki Maeyashiki, Nobuharu Tamaki, Yutaka Yasui, Yuka Takahashi, Hiroyuki Nakanishi, Masayuki Kurosaki, Namiki Izumi
Journal: Journal of Clinical Oncology (2023)

542 Background: Comprehensive genomic profiling (CGP) using tissue and blood specimens is covered by national health insurance for patients who have already received standard systemic therapy in Japan. We investigated the clinical utility of CGP in patients with unresectable primary liver cancer in real-world practice. Methods: We retrospectively investigated the clinical outcome of the patients with unresectable primary liver cancer. All patients received CGP between February 2021 and May 2022 at our institution. Results: 17 patients with unresectable primary liver cancer were included. 10 patients had hepatocellular carcinoma (HCC) and seven had intrahepatic cholangiocarcinoma (ICC). In HCC patients, the treatment line at CGP was 4th (n=5), 5th (n=4), and 6th-line (n=1). The samples were from liver tumor biopsy (n=2), surgical specimens of bone metastases (n=2), and blood (n=6). Clinically meaningful oncogene mutations were detected in all HCC cases. Seven of 10 patients were candidates for clinical trials, and 1 patient showed TMB-high. Six of the 7 patients could not participate in clinical trials due to renal dysfunction, low platelet counts, the immune-related adverse event of past therapy, or HBV infection. One patient with TMB high started pembrolizumab. In ICC patients, the treatment line at CGP was 1st (n=6), and 2nd -line (n=1). The samples were from liver tumor biopsy (n=5), blood (n=1) and surgical specimens of lung metastases (n=1). Clinically meaningful oncogene mutations were detected in all ICC cases. Six of 7 patients were candidates for clinical trials, and 1 patient showed MSI-high. One patient with MSI high started pembrolizumab, and one patient with FGFR2 fusion could use pemigatinib as 3rd line. The Overall survival duration of this patient with ICC (StageⅣB) was 26 months. In total, 13 of 17 patients were candidates for clinical trials, and 4 of 17 patients could receive personalized therapy according to the results of CGP. Conclusions: CGP in patients with unresectable primary liver cancer was useful in real-world practice. However, most patients could not participate in clinical trials because of adverse events associated with previous therapies. The best timing of CGP should be discussed in the future to provide more personalized therapies.
Clinical outcomes of appendix goblet cell adenocarcinoma and role of systemic chemotherapy.
Authors: Madeleine Cornelia Strach, Bipasha Chakrabarty, Raghavendar Nagaraju, Omer Aziz, Sarah O'Dwyer, Jorge Barriuso
Journal: Journal of Clinical Oncology (2023)

50 Background: Appendix goblet cell adenocarcinomas (GCA) are rare aggressive tumours with patients often presenting with peritoneal metastases. Cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) can be curative treatment and the role of systemic chemotherapy less defined. There is a need to better understand factors that predict outcome alongside assessment of the latest WHO 2019 classification. Methods: Demographics, clinicopathological variables, treatment characteristics and survival of patients with GCA from a UK peritoneal tumour centre were identified through a prospective database (2005-2021). Patients were selected for CRS/HIPEC based on disease burden. Pathology records were reviewed and those previously classified by Tang grading were reclassified to WHO 2019. The primary endpoint was overall survival (OS). Analysis was by the Kaplan-Meier method. Results: We identified 177 patients with GCA who had a median follow-up of 67 months (m, 4-207). Mean age at diagnosis was 57 years (22-79) and 88 were female (50%). There were 99 patients (56%) who had localised disease (M0) and 74 (42%) who had metastatic disease (M1). There were 126 (71%) patients who had CRS and 115 (91%) had HIPEC (65% MMC, 25% Oxaliplatin); median peritoneal cancer index score was 1 (0-28) and 12 (10%) patients had M1 disease. There were 72 (41%) patients who had systemic chemotherapy (72% oxaliplatin with fluoropyrimidine) and of those who had CRS, four had neoadjuvant, 18 adjuvant and the rest palliative intent chemotherapy. Incomplete CRS resulted in shorter OS compared to complete CRS (median 23 v 103m, p&lt;0.001). Patients with involved nodes had shorter OS (32m v not reached, NR, p&lt;0.001) compared to those with uninvolved nodes. WHO 2019 grade 2 predicts for longer OS than Tang B (median 118 v 54m, p=0.031). The table shows univariate survival according to grade and chemotherapy. Conclusions: This study represents the largest series of pure appendix GCA with long term follow-up data. Patients with positive lymph nodes and incomplete CRS had poor survival outcomes. The WHO 2019 classification had no direct prognostic correlation with the previous Tang classification. WHO 2019 grade 2 had longer OS compared to Tang B suggesting further stratification of the grade 2 group could be considered. Patients who had systemic chemotherapy had shorter OS and DFS as expected based on the selection of patients with higher grade, lymph node involvement and higher disease burden as part of clinical practice. [Table: see text]
Short-term outcomes of robotic gastrectomy vs laparoscopic gastrectomy for patients with gastric cancer: A randomized clinical trial.
Authors: Toshiyasu Ojima, Keiji Hayata, Junya Kitadani, Taro Goda, Shinta Tominaga, Masaki Ohi, Hiroki Yamaue, Manabu Kawai
Journal: Journal of Clinical Oncology (2023)

344 Background: Robotic gastrectomy (RG) procedure for gastric cancer (GC) patients may be associated with decreased incidence of intra-abdominal infectious complications. Prospective randomized controlled trials (RCTs) comparing laparoscopic gastrectomy (LG) and RG are required, however. We completed an RCT to compare short-term surgical outcomes of LG and RG for GC patients. Methods: This was a randomized, two-center clinical trial. All included patients are adults with primary carcinoma of the stomach, in whom the tumor is considered surgically resectable (cStage I-III). Included in this trial were 240 patients with GC. The primary endpoint was to assess the incidence of postoperative intra-abdominal infectious complications including pancreatic fistula, intra-abdominal abscess, and anastomotic leakage. Secondary endpoints included incidence of postoperative complications, surgical results, postoperative course, and oncological outcomes. Lymphadenectomy without touching the pancreas was basically performed during robotic gastrectomy using assisting articulating forceps. Results: A total of 241 patients were randomly assigned to the LG group (n = 122) or the RG group (n = 119), and 236 patients (LG119 RG117) were analyzed for ITT population. Overall incidence of intra-opereative infectious complications higher than Clavien-Dindo grade II were not significantly different (LG 8.4%, RG 6%). However, overall incidence of any complications higher than grade II were significantly lower in the RG group (19.3 vs 8.5% P = .019). In RG group, postoperative pancreatic fistula was not found. Amylase levels in drainage fluid on POD 1 were significantly lower in the RG group (893IU/L) than in the LG group (438 IU/L) ( P = 0.039). Conclusions: Regarding short-term surgical outcomes, RG is feasible, safe and ideal treatment procedure for GC. Our RG procedure without touching the pancreas may be associated with decreased incidence of postoperative pancreatic fistula. Clinical trial information: UMIN000031536 .
Role of pretreatment absolute lymphocyte count in survival outcomes for esophageal cancer treated with neoadjuvant chemoradiotherapy and pembrolizumab: An analysis from a prospective cohort.
Authors: Weixiang Qi, Xiaoyan Wang, Jiayi Chen, Shengguang Zhao, Hecheng Li
Journal: Journal of Clinical Oncology (2023)

338 Background: To analyze the relationship between pre-treatment inflammatory biomarkers (IBs) and survival outcomes for ESCC treated with neo-CRT and pembrolizumab. Methods: Clinical variables and IBs [absolute monocyte count (AMC), absolute lymphocyte count (ALC), platelet count (PLT), neutrophil lymphocyte ratio (NLR), Platelet lymphocyte ratio (PLR), Lymphocyte monocyte ratio (LMR), Pan-Immune Inflammation value (PIV), Systemic immunoinflammatory index (SII), Systemic Immunoreactivity Index (SIRI) and prognostic nutritional index (PNI)] were collected from two prospective trials. Univariate and multivariate analysis was performed. Results: A total of 51 patients were included. Of them, 35 patients achieved pathologic complete response after neo-CRT and pembrolizumab (pCR: 68.6%). With a median follow-up of 20 months, the two-year PFS and OS of the cohort was 64% and 91%, respectively. Multivariate logistic regression analysis indicated that ALC (OR 4.4, p=0.051) and PLT (OR 6.7, p=0.023) were two independent predictors for achieving pCR among ESCC treated with neo-CRT and pembrolizumab. Multivariate Cox regression analysis showed that ALC (HR 0.27, p=0.028) and SIRI (HR 3.13, p=0.048) were two independent predictors for PFS of this patient population. K-M analysis demonstrated that the PFS of ESCC with high base line ALC was significantly better than those with low ALC (2-year PFS: 77% vs. 47%, p=0.027), but not for overall survival (2-year OS: 96% vs. 87%, p=0.46). Conclusions: Our data demonstrates that pre-treatment ALC is an independent predictor for archiving pCR and favorable outcomes of ESCC treated with neo-CRT and pembrolizumab. Clinical trial information: NCT04435197 ; NCT04435197 .[Table: see text]
Efficacy and safety of anlotinib with PD-1 inhibitors in the treatment of advanced hepatocellular carcinoma: A real-world study.
Authors: Kehe Chen, Xianshi Huang, Lei Yu, Jianxun Lu, Fei Huang, Zhiguang Wang, Yan Wei, Encun Hou, Min Luo, Shiqing Huang, Hongbo Hu, Mei Ou
Journal: Journal of Clinical Oncology (2023)

583 Background: The IMbrave 150 study opened the door of immuno-oncology (IO) combined with targeted therapy in patients (pts) with hepatocellular carcinoma (HCC). At present, some other combination of IO and tyrosine kinase inhibitors (TKIs) had been proved as efficient regimens in China and there are many ongoing studies on this approach with preliminarily considerable efficacy. Furthermore, the efficacy of this combination still needs to be explored in real-world patients. The aim of this study is to explore the efficacy and safety of anlotinib plus PD-1 inhibitors in the treatment of HCC in real-world. Methods: This is a multi-center, prospective real-world study in pts (N=200) diagnosed as advanced HCC, who evaluated by physician would get benefits from anlotinib alone or in combination with PD-1 inhibitors. The enrolled patients received treatment according to physicians. Clinical efficacy was summarized, and adverse events were documented. Tumor response was assessed by investigators according to RECIST version 1.1. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and safety. Results: As of data cutoff date of Aug, 2022, a total of 119 patients were enrolled with a median age of 55 years (range 29-83). Among them 78% ECOG PS 0-1, 21% ECOG PS 2 and 1% ECOG PS 4. 75 pts received anlotinib plus PD-1 inhibitors as first-line treatment, 17 pts as second-line treatment and 7 pts as third-line and above. 76 patients were eligible for response evaluation. The ORR as best response was 11.8% (95%CI: 5.6%, 21.3%). The DCR was 73.7% (95%CI: 62.3%, 83.1%). The preliminarily results indicated that the median OS was 12.5 months (95%CI: 9.7, 15.4), the median PFS was 8.1 months (95%CI: 5.9, 10.3). Any grade treatment-related adverse events (TRAEs) observed in 50% of pts. The most common TRAEs were hypoalbuminemia (18.6%), hypertension (11.4%), decreased white blood cell count (11.4%) and decreased platelet count (10%). Conclusions: Present study indicated that the combination of anlotinib and PD-1 inhibitors exhibited potential efficacy and manageable adverse events in the treatment of advanced HCC in the real world. The conclusion should be validated in more patients included subsequently. Clinical trial information: NCT04954521 .
Comparison of liver-directed combined radiotherapy versus sorafenib in patients with locally advanced hepatocellular carcinoma with portal vein tumor thrombosis: An Asian Liver Radiotherapy Group Study.
Authors: Jinsil Seong, Jina Kim, Jason Chia-Hsien Cheng, Taek-Keun Nam, Jin Hee Kim, Wen-Yen Huang, Hiroshi Aikata, Myungsoo Kim, Jinbo Yue, Victor Ho-Fun Lee, Zhaochong Zeng
Journal: Journal of Clinical Oncology (2023)

565 Background: While systemic treatment is the mainstay for advanced hepatocellular carcinoma (HCC), numerous studies have highlighted the added value of local treatment. This study aimed to investigate the clinical efficacy of liver-directed combined radiotherapy (LD-CRT) compared to sorafenib, a recommended treatment until recently in locally advanced HCC presenting portal vein tumor thrombosis (PVTT) using a multinational patient cohort. Methods: We identified HCC patients presenting PVTT treated with either sorafenib or LD-CRT in 10 tertiary hospitals over Asia during 2005-2014. Propensity score matching (PSM) was performed to minimize the imbalance in patient and tumor characteristics of the two groups. The primary endpoint was overall survival (OS), and secondary endpoints were distant metastasis free survival (DMFS), local failure free survival (LFFS), and treatment related toxicity. Results: Total 1,035 patients including 360 patients in the sorafenib group and 675 patients in the LD-CRT group were enrolled. The majority of patients in the sorafenib group received 400 mg of sorafenib twice a day initially, and the dose was reduced to 50% or 25% if adverse reactions were noted. LD-CRT was given in liver-directed concurrent chemoradiotherapy in 502 (74.4%) patients, followed by transarterial chemoembolization plus radiotherapy in 149 (22.1%) patients. After PSM, 336 patients from each group were matched, and all features were well balanced between the two groups. At a median follow up of 28.8 months (interquartile range, 16.5-63.6), the median OS was 11.0 and 17.1 months for the sorafenib and LD-CRT groups, respectively ( p=0.001). In addition, LD-CRT group showed significantly improved DMFS and LFFS compared to the sorafenib group (median DMFS 14.9 vs 9.6 months, p=0.004, and median LFFS 15.7 vs 9.6 months, p=0.002). Conversion rate to curative surgery was significantly higher in the LD-CRT group (8.6% vs 0.9%, p=0.002). Those who underwent surgery had younger median age (54 vs 59, p=0.024), smaller median tumor size (6.5 cm vs 8.9 cm, p=0.012), and more unilateral disease (75.0% vs 43.8%, p&lt;0.001). OS and LFFS were significantly prolonged in patients who underwent surgical treatment. Grade 3 or higher toxicity was more frequently noted in the sorafenib group compared to the LD-CRT group (7.7% vs 0.7%, p&lt;0.001). Conclusions: Analysis of a propensity score matched multinational patient cohort revealed that liver-directed combined RT improved survival outcomes of locally advanced HCC patients presenting PVTT. While further prospective studies are warranted, we carefully suggest active multimodal local treatment for locally advanced HCC presenting PVTT.
STELLAR-303: A phase 3 study of XL092 in combination with atezolizumab versus regorafenib in patients with previously treated metastatic colorectal cancer (mCRC).
Authors: J. Randolph Hecht, Josep Tabernero, Aparna Raj Parikh, Yijia Wang, Zhong Wang, Martin Schwickart, Dominic Curran, Anwaar Saeed
Journal: Journal of Clinical Oncology (2023)

TPS267 Background: The prognosis of patients with mCRC is poor, with a 5-year survival rate of 14% (American Cancer Society 2020). Patients who have progressed after front-line chemotherapy have limited treatment options. Regorafenib or trifluridine-tipiracil are approved for patients in the third- or later-line setting, but survival benefit is limited. While immune checkpoint inhibitor (ICI) therapy is approved (nivolumab ± ipilimumab, and pembrolizumab) in patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) mCRC, the MSI-H phenotype is limited to ~5% of mCRC patients. In phase 1/2 trials, ICIs in combination with VEGFR2 multi-kinase inhibitors (MKIs) have demonstrated encouraging clinical activity in mCRC, including atezolizumab and durvalumab (ICIs) in combination with the MKI cabozantinib, with data suggesting a greater benefit in RAS wild-type (wt) vs mutant (mut) disease (Abrams TA, et al. ASCO GI 2022:Abs 121; Saeed A, et al. ASCO GI 2022:Abs 135). XL092 is a novel MKI, targeting MET, VEGFR2, and the TAM kinases AXL and MER; the relatively short half-life (~21 hours) of XL092 is favorable for once-daily (QD) dosing and dose modification to manage tolerability. STELLAR-303 is a phase 3 study evaluating the efficacy and safety of XL092 + atezolizumab versus regorafenib in patients with previously treated RASwt or RASmut mCRC. Methods: STELLAR-303 (XL092-303; NCT05425940) is a global, open-label, randomized phase 3 study. Eligible patients are ≥18 years old and have mCRC that is measurable per RECIST v1.1, are documented not to have MSI-H or dMMR disease, and have an ECOG performance status of 0–1 and adequate organ function. RAS and MSI/dMMR status must be determined by a tissue-based analysis. Patients must have progressed during/after or be intolerant to standard-of-care treatments for mCRC; prior regorafenib, trifluridine/tipiracil, or PD-L1/PD-1 ICIs are not allowed. Patients are randomized 1:1 to XL092 100 mg PO QD + atezolizumab 1200 mg IV Q3W or to regorafenib 160 mg PO QD (21 days of 28-day cycle); randomization is stratified by geographic region (Asia vs other), RAS status (wt vs mut), and liver metastases (yes/no). The study plans to enroll 600 patients (400 RASwt and 200 RASmut). The primary endpoint is overall survival in the RASwt population, with additional efficacy endpoints of progression-free survival, objective response rate, and duration of response per RECIST v1.1 by investigator; efficacy endpoints will also be assessed in the overall study population and in patients with RASmut mCRC. Additional endpoints will assess safety, quality of life, changes in biomarkers, pharmacokinetics, immunogenicity of atezolizumab, and healthcare utilization. Enrollment is ongoing. Clinical trial information: NCT05425940 .
Systemic anti-cancer therapy in older patients with gastrointestinal malignancies following comprehensive geriatric assessment: An age-based subgroup analysis.
Authors: Caitriona Goggin, Darren J Walsh, Michelle Hannan, Carol Buckley, Emmet Jordan, Paula Calvert, Miriam O'Connor, Anne Horgan
Journal: Journal of Clinical Oncology (2023)

796 Background: Comprehensive geriatric assessment (CGA) is recommended to inform treatment decisions in older patients with cancer. Patients ≥ 70 years are referred to the Geriatric Oncology and Liaison (GOAL) clinic in University Hospital Waterford, for a pre-treatment CGA, which includes assessment of mobility, cognitive, nutritional, functional, and psychological status, along with comprehensive geriatric pharmacological assessment. Informed treatment recommendations are made using CGA outcomes and risk assessed using the Cancer and Aging Research Group toxicity calculator. Limited information exists on treatment decisions based on age subgroups within the geriatric oncology population. Methods: Data from patients with gastrointestinal (GI) malignancies attending the GOAL clinic over a 3-year period to September 2022 were included. Patients ≥ 70 years with a G-8 (screening tool) score ≤14, and all patients aged ≥ 80 underwent CGA. An age-based subgroup analysis (&lt; 80 vs ≥ 80) of systemic anti-cancer therapy (SACT) decisions was performed using the Chi-square test. Results: In total, 206 patients with GI malignancies were assessed, comprising 67 (33%) patients with gastroesophageal cancer, 40 (19%) with pancreaticobiliary and 92 (45%) with colorectal cancer. 40% of patients were ≥ 80 years (n = 83). The majority of patients had stage III/IV disease (82%, n = 168). Across all groups, 58% (n = 120) of patients were treated with SACT, comprising 70% of those &lt; 80 (n = 86) and 41% (n= 34) of those ≥ 80. Across all stages (I-IV), patients ≥ 80 years were less likely to be treated with SACT compared to patients &lt; 80 years (p &lt; 0.01). There was no significant difference between age groups when comparing treatment intent (curative vs palliative) (p = 0.15). There was no significant difference between age groups for baseline dose reductions vs full dose (p = 0.18). Patients ≥ 80 years were less likely to receive polychemotherapy regimens in comparison with the &lt; 80 subgroup (p &lt; 0.01). Conclusions: Older patients with GI malignancies are a heterogeneous population. In the setting of a CGA, patients ≥ 80 years are less likely to receive SACT across any stage group, and are more likely to receive monochemotherapy regimens. The use of CGA ensures a considered and personalised approach to identify older adults most likely to benefit from active treatment and those where best supportive care alone is more appropriate.
Tumor mutational burden as a potential predictive marker for the efficacy of immunotherapy in advanced gastric cancer.
Authors: Jae Yeon Jang, Sun Young Jeong, Seung Tae Kim
Journal: Journal of Clinical Oncology (2023)

324 Background: Tumor mutational burden (TMB) is known as an independent predictive factor in predicting treatment response of immunotherapy. We aimed to evaluate the efficacy of immunotherapy in advanced gastric cancer (AGC) according to TMB and other markers. Methods: The patients with AGC, aged ≥ 18, who received pembrolizumab or nivolumab from October 1, 2020, to July 27, 2021, at Samsung medical center in Korea, were analyzed retrospectively. TMB was measured by next-generation sequencing-based assays, and PD-L1 is tested using immunohistochemical assay 22C3 pharmDx. Referring to the results of previous studies, TMB-high was defined as 14.31 mutations/megabase (mt/Mb) or above. Results: A total of 54 AGC patients who were treated with immunotherapy, pembrolizumab or nivolumab, were analyzed. Seven patients were TMB-high, and 47 patients were TMB-low. Compared to TMB-low group, TMB-high group showed higher overall response rate (ORR) (42.9% vs 6.4%, p=0.023), and disease control rate (66.7% vs. 22.9%; p=0.033). The median OS was longer in the TMB-high group with 22.4 months (95% CI, 19.738-25.115), while the TMB-low group with 3.6 months (95% CI, 2.109-5.104; p=0.020). In addition to TMB, microsatellite status was statistically significantly associated with the efficacy of immunotherapy in AGC. Microsatellite instability group had better ORR (n=3/4, 75%) compared to microsatellite stable group (n=4/50, 8.0%; p=0.005). Other than that, the ORR of the patients whose PD-L1 CPS was 1 or above did not differ from the patients whose PD-L1 CPS was lower than 1. Although there was no statistical significance, among TMB-low patients, PD-L1 CPS ≥1 group numerically exhibited a higher overall response rate (13.0% vs 4.0%; p=0.338). Conclusions: In our analysis, the cut-off value of TMB was set to 14.31mb/Mt, and TMB-high was associated with the better ORR and OS of immunotherapy in AGC. TMB could be a potential predicting marker for a therapeutic response of immunotherapy in AGC.[Table: see text]